The long-range objectives of the proposed research are to contribute to the complete understanding of the pathogenesis and immunology of cholera. As cholera is the prototype model of an emerging group of enterotoxic enteropathies, the results should be applicable to other secretory diarrheas. Our major specific immediate goals are (1) to develop additional mutants or genetic hyybrids of Vibrio cholerae which are stably avirulent but which can colonize the gut and elicit local antibacterial and antitoxic immunity; (2) to delineate the mechanism which enables cholera vibrios to adhere to the epithelium of the small bowel and (3) to continue our studies on the synthesis and structure of the cholera enterotoxin in relation to its mode of action and immunology.